Investigating Molecular Differences related to T-bet-Positive Tumor-infiltrating Lymphocytes in Axillary Node-negative Breast Cancer

The clinical outcomes of axillary node-negative (ANN) breast cancer (BC) patients were previously shown to be positively associated with T-bet+ tumor-infiltrating lymphocytes (TILs). This study identified differences in miRNA and gene expression, and in PD-L1 expression between T-bet+/high and T-bet-/low tumors that provided insights into how T-bet+ TIL- mediated immunesurveillance may relate to tumor characteristics and disease outcome in ANN BC. The differentially expressed (DE) miRNAs were associated with intrinsic cancer-related pathways and immune-modulatory activities. miR-135a, in particular, was downregulated in T- bet+/high tumors, and was shown to be a direct suppressor of CXCL10, a T lymphocyte-recruiting chemokine. Among the DE genes, BRD4, a co-activator of NF-kB, was upregulated in T-bet+/high tumors at both mRNA and protein levels, suggesting a link between BRD4 expression and T-bet+-TIL-mediated inflammatory activities. The mRNA expression of PD-L1, a T-cell inhibitory marker, was associated with T-bet+ TILs, and basal subtype.M.Sc